Patent GB-808952-A (GB)
Title: Improvements in or relating to amines and to processes for their preparation
Inventor: ASHLEY JULIUS NICHOLSON
Filed: 1954-09-25
Abstract: The invention comprises amides of the formula: <FORM:0808952/IV (b)/1> where R1 and R2 are the same or different and are hydrogen, an alkyl group of not more than 6 carbon atoms, or an hydroxyalkyl group, R3 is an aromatic or aliphatic acyl group, R4 is an alkyl or aryl group and A is an unbranched chain of 5 to 9 methylene groups, salts thereof with acids, and sodium formaldehyde bisulphite compounds of primary amines of the above formula.  Salts mentioned are the hydrohalides and methane sulphonates.  The amides are made by reacting a compound of the formula: <FORM:0808952/IV (b)/2> with a compound Q, P and Q being such that a group -O-A-Y is formed in the paraposition to X, X being a tertiary amine group -NR1R2 or an atom or group convertible to a primary, secondary or tertiary amine group -NR1R2, and Y being -NR3R4 or an atom or group convertible thereto, the convertible atoms or groups being transformed into the desired final group or groups.  X may be an acylamido, carbonamido, nitro, nitroso, alkoxycarbonylamido, anil, arylazo, acylalkylamido or quaternary ammonium group, and Y may be N-methylacetamido, N-methylbenzamido, N-phenylbenzamido, acetamido, benzamido, benzenesulphonamido or nitro.  Further, X may be hydrogen when a nitro group is introduced by nitration, reduced to amino and alkylated if desired.  Specific embodiments of the process are: (1) the reaction of the compound <FORM:0808952/IV (b)/3> with a compound HalR4 where Hal is halogen and R4 is alkyl; (2) the acylation of <FORM:0808952/IV (b)/4> with an acid, acid halide or anhydride capable of introducing acyl group R3; (3) the reaction of <FORM:0808952/IV (b)/5> where Z is the radical of a reactive ester such as a halogen atom with a compound MNR3R4 where M is hydrogen or an alkali-metal; and (4) the reaction of <FORM:0808952/IV (b)/6> with Z-A-NR3R4.  In examples, (1) 5-p-nitrophenoxypentyl bromide and aniline yield 1 - p - nitrophenoxy - 5 - anilinopentane which with benzoyl chloride gives 1-p-nitrophenoxy-5 - (N - phenylbenzamido) pentane, reduced with H2/Pt to 1-p-aminophenoxy-5-(N-phenylbenzamido) pentane; (2) N-methyl-N-5-bromo-pentyl-benzamide, made from N-methylbenzamide and 1:5-dibromopentane, is treated with potassium p-nitrophenoxide to yield 1-p-nitrophenoxy - 5 - N - methylbenzamidopentane which is reduced to the corresponding amino compound; (3) 1-p-nitrophenoxy-5-benzenesulphonamidopentane, made by reacting benzene sulphonyl chloride with 5-amino-1-p-nitrophenoxy-pentane, is alkylated with methyl iodide to give 1-p-nitrophenoxy-5-N-methylbenzenesulphonamidopentane which is reduced to the amine, similarly 1-p-nitrophenoxy-5-N-methylmethanesulphonamidopentane and the corresponding amino compound are prepared; (4) 1 - p - nitrophenoxy - 5 - anilinopentane and methanesulphonyl chloride give 1-p-nitrophenoxy - 5 - N - phenylmethanesulphonamidopentane which is reduced to the amine; (5) 1 - p - di - (2 - hydroxyethyl) aminophenoxy - 5 - N-methylmethanesulphonamidopentane is made by reacting ethylene chlorhydrin with the corresponding 1-p-diamino compound; (6) N-methylbenzene sulphonamide is treated with 5-(p-nitrophenoxy) pentyl bromide in presence of sodium, and the nitro compound obtained is reduced to give 1-(p-aminophenoxy)-5-(N-methylbenzenesulphonamido) pentane, the corresponding hexane and octane homologues being similarly prepared; (7) N-methylbenzene sulphonamide is reacted with 1:5-dibromopentane and the product treated with potassium p-nitrophenoxide to give 1-(p-nitrophenoxy)-5-(N - methylbenzene sulphonamide) pentane which is reduced to the corresponding amino compound; (8) 1-(p-dimethylaminophenoxy)-6-(N - methylbenzene sulphonamido) hexane is made by methylation of the 1-(p-aminophenoxy) compound.  The Provisional Specification also refers to compounds of the above general formula where in addition to the values of R1, R2, R3, R4\t and A given above, R1 and/or R2 may be alkoxy alkyl, R3 may be a heterocyclic acyl group, R4 may be analkyl, cycloalkyl or a heterocyclic group, and A may be substituted by one or more alkyl groups of up to 6 carbon atoms and may contain one or more ethylenic linkages. Specification 769,706 is referred to.ALSO:Compositions for use in the treatment of bilharziasis comprise a compound of the formula:  <FORM:0808952/VI/1> where R1 and R2 are the same or different and are hydrogen, an alkyl group of not more than 6 carbon atoms, or a hydroxyalkyl group, R3 is an aromatic or aliphatic acyl group, R4 is an aryl or alkyl group and A is an unbranched chain of 5 to 9 methylene groups, or salts thereof with acids, together with a liquid diluent such as water, or a solid diluent such as starch, lactose, talc, stearic acid, magnesium stearate or gums.  Examples of typical compositions given are (a) 1-p-aminophenoxy-5-(N-phenylbenzamido) pentane, starch, dextrin, magnesium stearate, stearic acid and sodium carboxymethyl cellulose, and (b) 1-p-aminophenoxy - 5 - (N - methylbenzamido) - pentane, starch, dextrin, magnesium stearate, stearic acid, alginic acid and sodium lauryl sulphate.  The compositions may be used in elixir, tablet, powder or capsule form.  Specification 769,706 is referred to.